A calcimimetic agent acutely suppresses parathyroid hormone levels in patients with chronic renal failure. Rapid communication.
The control of hyperparathyroidism in patients with chronic renal failure continues to be a problem, particularly when parathyroid hormone (PTH) suppression becomes refractory to calcitriol activation of parathyroid cell 1,25-dihydroxyvitamin D receptors. To evaluate whether parathyroid cell calcium receptor activation may be useful in suppressing PTH levels, we tested the safety and effectiveness of a novel calcimimetic agent in dialysis patients with hyperparathyroidism. In a prospective, dose finding study, the calcimimetic agent, NPS R-568, was administered orally to seven patients at the start of a hemodialysis session and again 24 hours later. Plasma PTH, calcitonin and ionized calcium levels were measured over a 48 hour period and patients were observed for adverse events. Plasma PTH levels fell abruptly in all patients after a single dose of the compound, with the maximum suppression occurring within one to two hours after its administration. Following the administration of low doses (40 or 80 mg), the suppressed PTH levels rose to baseline values over 48 hours, whereas in patients who received high doses (120 or 200 mg) the mean PTH level remained 51% below baseline. Plasma calcitonin increased after the administration of both low and high doses (peak effect within 4 to 6 hr), with levels always returning to baseline by 48 hours. There were no episodes of hypocalcemia and no adverse effects were reported. We conclude that the activation of parathyroid cell calcium receptors by a novel calcimimetic compound is safe and effective in acutely suppressing PTH secretion in dialysis patients with hyperparathyroidism. Whether concomitant stimulation of calcitonin secretion will provide added beneficial effects on bone remodeling remains to be determined in long-term studies.
Antonsen
J E
JE
Department of Medicine, Veterans Affairs Medical Center, Seattle, Washington, USA.
Sherrard
D J
DJ
Andress
D L
DL
D000328:Adult; D000368:Aged; D000814:Aniline Compounds / Q000627:therapeutic use*; D002116:Calcitonin / Q000097:blood; D002118:Calcium / Q000819:agonists* / Q000097:blood; D006801:Humans; D006961:Hyperparathyroidism / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D010627:Phenethylamines; D011437:Propylamines
D000814:Aniline Compounds; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010281:Parathyroid Hormone; D010627:Phenethylamines; D011437:Propylamines; D002116:Calcitonin; D002118:Calcium